Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
Photodiagnosis Photodyn Ther. 2018 Dec;24:1-6. doi: 10.1016/j.pdpdt.2018.06.024. Epub 2018 Jun 28.
Topical 5-aminolevulinic acid mediated photodynamic therapy (PDT) is known to be an effective method in treating acne vulgaris and other sebaceous gland-related diseases. The therapeutic mechanisms of ALA-PDT still remain undetermined. Our team has reported that ALA-PDT suppressed the cell growth in SZ95 sebocytes by mTOR-p70 S6K signaling. In this study, we aimed to investigate upstream of the mammalian target of rapamycin (mTOR) signaling cascade after ALA-PDT on cell growth of human SZ95 sebocytes.
Human SZ95 sebocytes were treated with different concentration of 5-ALA PDT. Western blotting was used to detect and analyze the protein expression level of P-Akt (T308)/Akt, P-Akt (S473)/Akt, P-Erk/Erk, P-AMPKα (T172)/AMPK, P-AMPKα1 (S485)/AMPKα2 (S491)/AMPK, P-PRAS40/PRAS40, RagC. Meanwhile, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences of P-p70 S6K/p70 S6K after ALA-PDT.
mTOR pathway inhibitor rapamycin decreased the level of P-p70 S6K reduced by ALA-PDT. Conversely, mTOR pathway activator IGF-1. ALA-PDT reduced the level of P-Akt (T308), P-Erk, P-AMPKα (T172), P-AMPKα1 (S485)/AMPKα2 (S491) and P-PRAS40, and no change was observed in the level of Rag C.
ALA-PDT suppresses the cell growth in SZ95 cells through Akt-/Erk- mTOR -p70 s6k pathway rather than PRAS40-/RagC- mTOR pathway.
局部 5-氨基酮戊酸介导的光动力疗法（PDT）已被证实是治疗寻常痤疮和其他与皮脂腺相关疾病的有效方法。ALA-PDT 的治疗机制仍未确定。我们的团队已经报道过，ALA-PDT 通过 mTOR-p70 S6K 信号通路抑制 SZ95 皮脂腺细胞的生长。在这项研究中，我们旨在研究 ALA-PDT 后，人 SZ95 皮脂腺细胞中雷帕霉素哺乳动物靶标（mTOR）信号级联的上游。
用不同浓度的 5-ALA PDT 处理人 SZ95 皮脂腺细胞。采用 Western blot 检测和分析细胞生长中 P-Akt（T308）/Akt、P-Akt（S473）/Akt、P-Erk/Erk、P-AMPKα（T172）/AMPK、P-AMPKα1（S485）/AMPKα2（S491）/AMPK、P-PRAS40/PRAS40、RagC 的蛋白表达水平。同时，加入 mTOR 通路激活剂 IGF-1 和 mTORC1 抑制剂 rapamycin，观察 ALA-PDT 后 P-p70 S6K/p70 S6K 的干扰情况。
mTOR 通路抑制剂 rapamycin 降低了 ALA-PDT 降低的 P-p70 S6K 水平。相反，mTOR 通路激活剂 IGF-1。ALA-PDT 降低了 P-Akt（T308）、P-Erk、P-AMPKα（T172）、P-AMPKα1（S485）/AMPKα2（S491）和 P-PRAS40 的水平，而 Rag C 的水平没有变化。
ALA-PDT 通过 Akt-/Erk-mTOR-p70 s6k 通路而非 PRAS40-/RagC-mTOR 通路抑制 SZ95 细胞的生长。
